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Biomedical subjects

A L Clark

Publications and source records attributed to A L Clark.

At least 109 records · Page 6Linked to original sources

Muscle fatigue and dyspnoea in chronic heart failure: two sides of the same coin?

The pathogenesis of the limiting symptoms in patients with chronic heart failure, shortness of breath and fatigue on exercise, are poorly understood. We analysed data from 222 incremental symptom limited exercise tests to determine whether there were differences between patients stopped by breathlessness or fatigue. One hundred and sixty patients were stopped by breathlessness and 62 by fatigue. There was no differences between the two groups in underlying diagnosis or in exercise performance (peak oxygen consumption 15.66 (+/- 5.62) ml.kg-1.min-1 in the fatigue group, 15.13 (+/- 4.64) in the breathless group). The ventilatory response as assessed by ventilatory response to carbon dioxide production (VE/VCO2 slope) was not different between the two groups (2.61 (+/- 0.96) in the fatigue group, 3.03 (+/- 1.23) in the breathless group: P = ns). There were no differences between the two groups in left ventricular dimensions, left ventricular ejection fraction or left ventricular end-diastolic pressure. The limiting symptoms of breathlessness and fatigue in chronic heart failure are two sides of the same coin. Any pathophysiological explanation of exercise limitation in chronic heart failure must unify these two symptoms.

Adolescent↗

Skeletal muscle and the control of ventilation on exercise: evidence for metabolic receptors.

Patients with chronic heart failure have an increased ventilatory response to exercise, and have metabolically abnormal skeletal muscle. It has been proposed that a neural signal to ventilation arising from exercising muscle may be heightened in chronic heart failure. Our objective was to detect evidence for such a signal in normal subjects by studying ventilatory behaviour during exercise with muscles in different metabolic states. Fifteen normal subjects undertook treadmill exercise both with and without cuffs inflated around each thigh to suprasystolic pressure. In a second experiment, a group of 11 normal subjects undertook cycle exercise using arms or legs at the same absolute work load. Metabolic gas exchange was measured using mass spectrometry with indicator gas dilution. The ventilatory response was greater at a given workload when subjects exercised with inflated cuffs. Oxygen consumption was reduced in keeping with the isolation of the exercising muscle bulk from the circulation. The ventilation/carbon dioxide output relationship was described by a linear regression function, but the slope of the relationship was increased by 25% from 20.9 (0.46) to 25.43 (0.73) (P < 0.001). Arm exercise at the same load as leg exercise resulted in unchanged oxygen consumption indicating that the same external work was being performed. There was an increase in ventilation at a given workload. The ventilation/carbon dioxide output slope was increased by 25% (from 21.9 (0.9) to 26.3 (0.8)) (P < 0.001). There is a signal to ventilation arising from exercising skeletal muscle which is enhanced by the ischaemia induced by cuff inflation during exercise. This signal appears to be neural.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ventilatory responses to exercise in adults after repair of tetralogy of Fallot.

BACKGROUND: Adult patients with total correction of tetralogy of Fallot may have poor exercise capacity associated with impaired right heart function and in particular pulmonary regurgitation. The ventilatory responses to exercise were studied in a group of such patients to assess relations between ventilation, exercise capacity, and right ventricular function. METHODS: 30 patients (7 female) (aged 27.8 (6.0) years) and 30 (7 female) controls of a similar age range were studied prospectively. All underwent exercise testing with metabolic gas exchange to determine peak oxygen consumption (peak VO2), and (as indices of the ventilatory response) the slope of the relation between both respiratory rate (RR) and ventilation (VE) against carbon dioxide production (VCO2). Patients were studied with pulsed wave Doppler echocardiography to determine pulmonary arterial systolic and diastolic flow characteristics. Patients were defined as having restrictive right ventricular function where diastolic pulmonary forward flow was seen coincident with atrial systole. RESULTS: In the group with tetralogy of Fallot mean (SD) peak VO2 was 35.3 (7.5) ml/kg/min (93.6 (15.3) % of expected for age, weight, height and sex). The RR/VCO2 slope was steeper in the Fallot group (6.8 (2.6) v 9.6 (4.7), P < 0.02). Those with restrictive right ventricles achieved a higher peak VO2 than those without (82.5 (10.1) % v 100.9 (13.8), P < 0.001). In the Fallot group alone, there was an inverse relation between ventilatory response and peak VO2 (RR/VCO2 v peak VO2; r = -0.63, P = 0.003: VE/VCO2 v peak VO2; r = -0.62, P < 0.001). CONCLUSIONS: Many of these patients with repaired tetralogy of Fallot had near normal exercise capacity, but as exercise capacity decreased, the ventilatory response to exercise increased. This was not due to alterations in pulmonary function tests or to the effects of cardiac size causing decreased lung volume. It may be that the increased ventilatory rate at a given level of carbon dioxide production acts as a respiratory pump aiding right ventricular function.

Adult↗

Anatomical dead space, ventilatory pattern, and exercise capacity in chronic heart failure.

BACKGROUND: Patients with chronic heart failure have an excessive ventilatory response to exercise, characterised by an increase in the slope of the relation between ventilation and carbon dioxide production (VE/VCO2 slope). Patients have an altered respiratory pattern with an increased respiratory rate (f) at a given tidal volume (VT), which may result in increased anatomical dead space ventilation. METHODS: The ventilatory responses in 88 patients with chronic heart failure and 43 age matched controls during maximal incremental treadmill exercise were analysed. Peak oxygen consumption (VO2), VE/VCO2 slope, and the slope of the relation between f and VT were derived. Anatomical dead space was estimated from a standard formula and anatomical dead space ventilation calculated. RESULTS: Peak VO2 was greater (mean (SD)) (33.2 (8.5) v 19.4 (6.7) ml/min/kg; P < 0.001) and the VE/VCO2 slope lower in the controls (25.96 (4.16) v 35.14 (9.80); P < 0.001). During matched submaximal exercise VT was higher (1.97 (0.92) v 1.68 (0.62) 1; P < 0.05) and flower in the controls (18.23 (6.48) v 24.28 (7.58); P < 0.001). At peak exercise there was no difference in f, but VT was higher in the controls (2.66 (0.97) v 1.90 (0.61) 1; P < 0.001). The VT/f slope was the same (0.04 (0.04)) in both groups. The intercept of the relation was greater for the control group (1.31 (1.28) v 0.59 (0.83); P < 0.001). Anatomical dead space ventilation was lower in the controls at submaximal work load (4.17 (1.56) v 5.58 (1.93) l/min; P < 0.001). At peak exercise anatomical dead space ventilation was the same in both groups, but was lower expressed as a percentage of total VE in the control group (9.8 (3.3) v 13.5 (4.0); P < 0.001). There were weak relations within the heart failure group alone between VT/f slope and peak VO2 and VE/VCO2 slope. CONCLUSIONS: The relation between anatomical dead space ventilation and VE/VCO2 slope is expected: as f increases, so do VE/VCO2 slope and anatomical dead space ventilation. The VT/f slope was the same in patients with chronic heart failure and controls, so change in respiratory pattern cannot explain the increase in VE/VCO2 slope. The stimulus causing the increased f has yet to be identified.

Case-Control Studies↗

Muscle metaboreceptors in hemodynamic, autonomic, and ventilatory responses to exercise in men.

A muscle metaboreceptor (ergoreceptor) contribution to the hemodynamic and autonomic responses to exercise is well recognized, but a ventilatory component remains controversial. Control handgrips were compared with handgrips followed by 4-min regional circulatory occlusion of the exercising muscles to isolate the metaboreceptor role in blood pressure, autonomic tone (spectral analysis of R-R and blood pressure variability), and ventilatory responses to exercise in 11 normal subjects. Exercise responses were maintained after the effort by metaboreflex activation in systolic pressure (136.2 +/- 3.5 vs. 123.0 +/- 4.3 mmHg, P < 0.05), ventilation (19.0 +/- 2.6 vs. 8.5 +/- 0.4 l/min, P < 0.0005), and sympathetic discharge to the heart and circulation (elevated low-frequency components of R-R interval, 1,747.5 +/- 309.2 vs. 1,085.9 +/- 259.1 ms2, P < 0.05, and systolic pressure variability, 45.3 +/- 3.9 vs. 26.5 +/- 4.4 mmHg2, P < 0.005). We conclude that metaboreflex contributes to the sympathetic, hypertensive, and hyperpneic responses to exercise in normal subjects.

Adult↗

Practice nurses' workload and consultation patterns.

BACKGROUND: There are calls for the role of the practice nurse to be developed and extended. Before areas for further training and education can be identified, baseline data are needed on practice nurses' current activity and workload. AIM: A study was undertaken to analyse the activity of practice nurses in two large inner city general practices and to assess the skills mix of the nursing staff required to meet the needs of the practices. METHOD: The study practices had a combined list of 26,000 patients, 80% of patients attracting a deprivation allowance. Each practice employed three practice nurses. A nurse activity index with 45 codes was constructed to describe patient-nurse consultations. Activity codes were categorized into traditional treatment tasks, extended role tasks or diagnosis and management tasks. For eight months, practice nurses in practices Y and Z recorded activity index codes for each patient consultation. Practice Y also recorded the source of referral and the age and sex of the patient. RESULTS: There were 13,898 practice nurse consultations during the study period, equivalent to an annual nurse consultation rate of 0.8 per patient. Compared with the practice population as a whole, the patients attending the practice nurses in practice Y were older (mean age 43 years versus 37 years, P < 0.001). Those attending the practice nurses in practice Y were also more likely to be female (61% of consultations were with female patients compared with 50% of the practice population as a whole, P < 0.001). In practice Y, patients referred themselves to the practice nurse in 42% of consultations, 32% were follow-up consultations and in 25% of cases the patient had been referred by a doctor. The most common reasons for nurse consultation were blood tests (15% of procedures in practice Y and 18% in practice Z) and dressings (13% in both practices). Most procedures in practices Y and Z were in the traditional treatment category (61%), 26% were in the extended role category and 9% in the diagnosis and management category (3% coded 'other', 1% uncoded). Between practices, the greatest difference in recorded procedures was for asthma check ups (7% of procedures in practice Y compared with 2% in practice Z). CONCLUSION: This study describes the workload of practice nurses in two inner city practices over eight months. Other practices could use the activity index to make comparisons over time and between practices. Up to 60% of nurses' work in the study practices could be done by a nurse without extended training and up to 30% could be done by a health care assistant, but with some loss of quality. It is suggested that half the nursing hours available to a practice should be offered by a nurse with extended training in order to undertake and develop extended role tasks and diagnosis and management tasks.

Adolescent↗

New evidence for improved survival in chronic heart failure.

Chronic heart failure is a common clinical syndrome with high associated mortality and morbidity. Recent advances in therapy for the condition with vasodilators and, in particular, angiotensin-converting enzyme inhibitors, have led to hopes for improvement in survival. Several large scale studies examining the role of vasodilators have reported over the last few years, and the role of vasodilators in the treatment and prevention of chronic heart failure is being delineated. There is new hope for patients with symptomatic heart failure; symptoms can be alleviated and prognosis improved. Increasingly, it appears as if there is a role for drug therapy in preventing the onset of chronic heart failure. In this paper, we examine the results of these studies and of some smaller studies in order to discuss the implications for current therapy and future research.

Chronic Disease↗

Insulin resistance in chronic heart failure.

The objective of this study was to investigate the existence of abnormalities of insulin sensitivity in patients with chronic heart failure. Glucose metabolism and insulin resistance were assessed in 10 male patients with severe, chronic heart failure and in 10 matched control subjects. Glucose, insulin and C-peptide concentration profiles were measured following a 0.5 g.kg-1 intravenous glucose tolerance test. Insulin sensitivity (inversely related to insulin resistance) was estimated by minimal modelling analysis of the glucose and insulin profiles. Heart failure patients had similar mean fasting plasma glucose concentration to controls but a significantly greater mean fasting plasma insulin concentration (P = 0.002) and C-peptide concentration (P = 0.02). Plasma glucose response profile was similar in the two groups but the incremental plasma insulin response profile of the heart failure group was significantly greater (P = 0.004). Mean insulin sensitivity was 73% lower in the heart failure patients (P = 0.003). These findings show that patients with severe chronic heart failure are hyperinsulinaemic and insulin resistant compared with a matched health group. This insulin resistance and hyperinsulinaemia may contribute to the progressive deterioration in myocardial function and associated clinical features of fatigue and reduced exercise tolerance seen in heart failure. Interventions designed to overcome or reduce insulin resistance warrant further investigation.

Blood Glucose↗

Predictors of exercise capacity in chronic heart failure.

Abnormalities of skeletal muscle rather than of haemodynamics may be important determinants of exercise capacity in chronic heart failure. We investigated an array of indicators of central haemodynamics and peripheral muscle function to establish which resting measurements predicted exercise performance. In 20 patients quadriceps strength, resting and peak leg blood flow and leg muscle cross sectional area were measured. In 18 patients average daytime blood pressure and pulse rate, haemodynamic variables at rest and during exercise, and autonomic activity were measured. There were correlations between peak oxygen consumption and quadriceps strength (0.65; P = 0.007), thigh muscle cross sectional area (r = 0.63; P = 0.004), and average daytime systolic blood pressure (r = 0.66; P < 0.01). There were no correlations with indices of peripheral blood flow, measures of haemodynamic function, or autonomic function. Quadriceps strength was the most important individual correlate of exercise tolerance (r = 0.73). With total muscle cross sectional area and left quadriceps strength also taken into consideration, 82% of the variation in peak oxygen consumption was explained. Of the haemodynamic variables, only average daytime systolic blood pressure predicted exercise performance. The resting variables that best predict exercise performance in chronic heart failure are measures of skeletal muscle function and bulk, and average daytime systolic blood pressure. These findings suggest that abnormalities in the periphery largely determine exercise performance in chronic heart failure, and that the ability of the heart to generate an adequate blood pressure response to daily activities is also predictive of functional status.

Autonomic Nervous System↗

Effects of motivation of the patient on indices of exercise capacity in chronic heart failure.

BACKGROUND: Measurement of variables of metabolic gas exchange during exercise is widely used to assess the severity of heart failure. The variables derived however, are potentially dependent on motivation of the patient and duration of exercise. METHODS: The data from exercise tests in 23 patients with exertional breathlessness were analysed to derive the following three common indices of exercise tolerance: anaerobic threshold, extrapolated maximum oxygen consumption, and the ventilation to carbon dioxide production slope. The data were reanalysed with the data points from the first 90% of subsequent exercise, the first 75%, and finally the data up to the point where a respiratory gas exchange ratio of 1 was reached. RESULTS: The mean (SEM) anaerobic threshold was lower when computed from 90% of the data points than from 100% (13.2 (1.0) ml/kg/min v 12.5 (1.0), p < 0.001) and lower still from 75% (11.4 (0.7), p = 0.006 v 90%). Extrapolated maximum oxygen consumption was unchanged when computed from 90% of the data, but higher when computed from 75% (25.4 (2.1) ml/kg/min at 100% v 28.6 (2.1) at 75%, p < 0.001). The slope of the ventilation to carbon dioxide production ratio became progressively shallower measured from 90% and 75% of eventual exercise: 32.3 (1.5) from 100% v 30.0 (1.5) from 90%, p < 0.001; and 28.3 from 75%, p < 0.001 v 90%. At a respiratory gas exchange ratio of 1, extrapolated oxygen consumption was unchanged from the final calculation, anaerobic threshold was lower than at 100% of exercise (11.8 (0.9), p = 0.005) and the ventilation to carbon dioxide production slope was shallower (27.5 (1.4), p < 0.001). CONCLUSIONS: Anaerobic threshold tends to overestimate severity of exercise limitation and extrapolated maximum oxygen consumption and the ventilation to carbon dioxide production slope tend to underestimate severity. Extrapolated maximum oxygen consumption is the most reliable of the three measures, and is independent of effort provided that patients are encouraged to exercise to the point where the respiratory gas exchange ratio exceeds 1.

Aged↗

Usefulness of arterial blood gas estimations during exercise in patients with chronic heart failure.

BACKGROUND: Coexisting cardiorespiratory disease may contribute in individual cases to the increased ventilatory response to exercise in patients with chronic heart failure. OBJECTIVE: To characterise further the arterial blood gas response to exercise and to explore the possible uses of blood gas sampling in clinical practice in patients with chronic heart failure. METHODS: 37 patients with a primary diagnosis of chronic heart failure (age (range) 59 (45-80); left ventricular ejection fraction 24.5% (4%-44%)) underwent exercise testing with arterial blood gas analysis during exercise. RESULTS: In 34 patients there was a small fall in arterial carbon dioxide tension from a mean (SEM) of 4.9 (0.1) kPa at rest to 4.6 (0.1) kPa at peak exercise (p < 0.001). There was no significant change in arterial oxygen tension. During the recovery period arterial oxygen tension rose from 13.3 (0.3) kPa at peak exercise to 14.8 (0.3) kPa three minutes into recovery (p < 0.001). Arterial carbon dioxide tension was unchanged. In the remaining three patients there was considerable arterial hypoxaemia on exercise, from 10.4 kPa at rest to 7.7 kPa at peak exercise. All of these patients had an alternative diagnosis (patent foramen ovale with right to left shunt during exercise, pulmonary embolic disease, and clinically unsuspected obstructive airways disease). CONCLUSION: Patients with a presumptive diagnosis of chronic heart failure should undergo exercise testing with arterial blood gas analysis. Arterial hypoxaemia on exercise is rare in stable chronic heart failure. If hypoxia on exercise is detected, an alternative diagnosis should be sought.

Aged↗

The role of right and left ventricular function in the ventilatory response to exercise in chronic heart failure.

BACKGROUND: Right ventricular function may be an important determinant of exercise capacity, peak oxygen consumption (VO2), and the ventilatory response to carbon dioxide production (VE/VCO2 relation) in patients with chronic heart failure (CHF). METHODS AND RESULTS: We studied the role of right ventricular function in CHF and also investigated the effects of absent right ventricular reserve in patients previously operated on with Fontan's procedure by measuring metabolic gas exchange during exercise in five groups of patients: (1) 10 patients who had previously undergone Fontan's procedure for congenital heart disease in whom the right ventricle is not functional; (2) 11 age-matched control subjects with dilated cardiomyopathy (DCM); (3) 15 age-matched normal subjects; (4) 42 patients with CHF; and (5) 16 age-matched control subjects. Left and right ventricular ejection fractions (LVEF and RVEF) were measured by radionuclide ventriculography in group 4. In the young subjects, the VE/VCO2 slope was lower in the control subjects than in the other two groups, being 24.4 +/- 4.3 against 33.3 +/- 6.6 in group 1 (P < .001) and 29.6 +/- 8.1 in group 2 (P < .05). The correlation between peak VO2 and VE/VCO2 was -0.80 (P = .005) in group 1 and -0.76 (P = .007) in group 2. In the older age groups, the VE/VCO2 slope was significantly greater (38.0 +/- 14.9 versus 25.4 +/- 3.7; P < .001) in the heart failure group (group 4). In neither control group was there a significant relation between peak VO2 and VE/VCO2 slope. In group 4, the relation between peak VO2 and VE/VCO2 was similar to that seen for groups 1 and 2. LVEF was 24.3 +/- 14.1%, and RVEF was 32.5 +/- 13.1%. There was no correlation between either RVEF or LVEF and peak VO2 or VE/VCO2 slope in the heart failure group. CONCLUSIONS: The relation between excessive ventilation and reduction in peak oxygen consumption is present in patients with no functioning right ventricle. RVEF is not a determining feature of either exercise capacity or the excessive ventilatory response in CHF.

Adult↗

Decreased heart rate variability in patients with chronic obstructive pulmonary disease.

To evaluate possible autonomic nervous system (ANS) dysfunction in patients with chronic obstructive pulmonary disease (COPD) in the absence of any hypoxic neuronal damage, we studied 31 patients with COPD patients aged 31 to 68 years (55 +/- 10) and 32 age-matched healthy subjects (control). Respiratory function in the patients was as follows: FEV1 = 52 +/- 8 percent; PaO2 = 71 +/- 14 mm Hg; and PaCO2 = 40 +/- 10 mm Hg. The ANS was assessed by heart rate variability (HRV) in the time domain (SD of mean RR interval) and frequency domain (autoregressive spectral analysis recognizing low [LF] and high [HF] frequency components, vagal and sympathetic related, respectively). Patients and controls were evaluated at rest and during vagal (controlled breathing [CB]) and sympathetic (passive head-up tilt) maneuvers. Patients with COPD showed a depressed global HRV (rest SD = 34 +/- 20 ms vs 45 +/- 15 ms, p < 0.05; tilt SD = 28 +/- 14 ms vs 38 +/- 13, p < 0.01) with a predominant respiratory drive (rest HF = 44 +/- 28 vs 28 +/- 18, p < 0.05; tilt HF 42 +/- 28 vs 16 +/- 12, p < 0.01) as compared with normal subjects. In the control group, vagal and sympathetic responses were in opposite directions following a stimulus, whereas there was no significant HRV response in the COPD group. We conclude that patients with COPD have abnormalities of ANS function, with in particular a depressed HRV response to sympathetic and vagal stimuli.

Adult↗

Ventilatory efficiency is unchanged after physical training in healthy persons despite an increase exercise tolerance.

BACKGROUND: In chronic heart failure, exercise training results in an improvement in exercise capacity and a reduction in the ventilatory response to exercise. The effects of a physical training programme on the ventilatory response in healthy persons is not known. METHODS: Metabolic gas exchange and ventilation were measured in 27 young healthy persons aged 31.4 +/- 7.6 years before and after a 19-week training programme of aerobic exercise; exercise was undertaken three times a week for 40 min. Ventilation, the slope of the relationship between ventilation and carbon dioxide production (VE-VCO2 slope) and the ventilatory equivalent for carbon dioxide were measured using respiratory mass spectroscopy. The peak expiratory flow rate in 1 s and forced vital capacity were also measured. RESULTS: Mean +/- SEM peak oxygen consumption increased from 39.5 +/- 1.5 to 45.4 +/- 1.7 ml/kg/min(P<0.001). Exercise time increased from 817 +/- 188 to 896 +/- 186 s (P<0.001). The respiratory exchange ratio at peak exercise was slightly lower after training: 1.30 +/- 0.02 compared with 1.36 +/- 0.03 (P = 0.02). Ventilation at equivalent stages of exercise was unchanged by training. The VE-VCO2 slope did not change (24.52 +/- 0.67 before training, 25.01 +/- 0.80 after training; NS). There was no change in the ventilatory equivalent for carbon dioxide either at rest (38.6 +/- 1.4 compared with 36.2 +/- 1.1; NS) or at its lowest point (23.3 +/- 0.6 compared with 22.9 +/- 3.2; NS). Neither exercise capacity nor the training response correlated with any of the measured ventilatory variables. CONCLUSION: In contrast to the situation in patients with chronic heart failure, there is no relationship between ventilatory variables and exercise capacity in healthy persons and no change in ventilatory performance as a result of physical training.

Adult↗

Skeletal muscle blood flow in heart failure measured by ultrafast computed tomography: validation by comparison with plethysmography.

OBJECTIVES: Abnormalities of skeletal muscle perfusion and metabolism may be important in the symptomatic limitation of patients with chronic heart failure. A method for assessing both skeletal muscle blood flow and mass would be useful in clinical practice and research. Ultrafast computed tomography has the potential to make these measurements. The aim was to determine the accuracy with which skeletal muscle blood flow could be measured by ultrafast computed tomography in patients with chronic heart failure. METHODS: Leg blood flow measured by venous occlusion plethysmography was compared with skeletal muscle blood flow by ultrafast computed tomography. Fourteen patients with chronic heart failure (aged 51 to 76 years) were investigated. Plethysmography and ultrafast computed tomography measurements were performed at rest and during hyperaemic flow induced by symptom limited bicycle exercise followed by five minutes of leg ischaemia. The ultrafast computed tomography measurements were made by analysing the opacification of the blood pool and of the muscle after an intravenous bolus of non-ionic radio-opaque contrast. RESULTS: Flows assessed by plethysmography ranged from 1.5 to 38.1 ml x 100 ml-1 x min-1. The slope of the line relating the two methods was 1.1 (95% confidence interval 0.91 to 1.31), and the mean (95% limits of agreement) of the differences between the two methods was 2.5(10.6) ml x 100 ml-1 x min-1. CONCLUSIONS: Ultrafast computed tomography is a useful tool in the measurement of both skeletal muscle mass and perfusion in humans.

Aged↗